| Autor: |
Lebbadi M, Julien C, Phivilay A, Tremblay C, Emond V, Kang JX, Calon F, Lebbadi, Meryem, Julien, Carl, Phivilay, Alix, Tremblay, Cyntia, Emond, Vincent, Kang, Jing X, Calon, Frédéric |
| Zdroj: |
Journal of Alzheimer's Disease; 2011, Vol. 23 Issue 1, p853-869, 17p |
| Abstrakt: |
Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3 × Tg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3:n-6 PUFA ratio upward in the brain (+11%, p < 0.001), including docosahexaenoic acid (DHA; +5%, p < 0.001) in 20 month-old mice. The expression of fat-1 decreased the levels of soluble Aβ₄₂ (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aβ₄₀ and Aβ₄₂ in the brain of 3 × Tg-AD mice. The 3 × Tg-AD/Fat-1 mice exhibited lower cortical levels of both soluble (-25%, p < 0.05) and insoluble phosphorylated tau (-55%, p < 0.05) compared to 3 × Tg-AD mice, but only in 20 month-old animals. Whereas a decrease of calcium/calmodulin-dependent protein kinase II was observed in 3 × Tg-AD/Fat-1 mice (-039%, p < 0.05), altered tau phosphorylation could not be related to changes in glycogen synthase kinase 3β, cyclin-dependent kinase 5, or protein phosphatase type 2A enzymatic activity. In addition, the expression of the fat-1 transgene prevented the increase of glial fibrillary acidic protein (-37%, p < 0.01) observed in 20 month-old 3 × Tg-AD mice. In conclusion, the expression of fat-1 in 3 × Tg-AD mice increases brain DHA and induces biomarker changes that are consistent with a beneficial effect against an AD-like neuropathology. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
